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Mitochondria, ATP, Glycolysis & Krebs Cycle

//Mitochondria, ATP, Glycolysis & Krebs Cycle

Mitochondria, ATP, Glycolysis & Krebs Cycle


Mitochondria are often referred to as the powerhouses of the cell. They help turn the energy we take from food into energy that the cell can use. But, there is more to mitochondria than energy production. Present in nearly all types of human cell, mitochondria are vital to our survival. They generate the majority of our adenosine triphosphate (ATP), the energy currency of the cell. Mitochondria are also involved in other tasks, such as signaling between cells and cell death, otherwise known as apoptosis.

The structure of mitochondria

Mitochondria are small, often between 0.75 and 3 micrometers and are not visible under the microscope unless they are stained. Unlike other organelles (miniature organs within the cell), they have two membranes, an outer one and an inner one. Each membrane has different functions. Mitochondria are split into different compartments or regions, each of which carries out distinct roles.

Mitochondrial disease

If mitochondria do not function correctly, it can cause a range of medical problems. The DNA within mitochondria is more susceptible to damage than the rest of the genome. This is because free radicals, which can cause damage to DNA, are produced during ATP synthesis. Also, mitochondria lack the same protective mechanisms found in the nucleus of the cell. However, the majority of mitochondrial diseases are due to mutations in nuclear DNA that affect products that end up in the mitochondria. These mutations can either be inherited or spontaneous. When mitochondria stop functioning, the cell they are in is starved of energy. So, depending on the type of cell, symptoms can vary widely. As a general rule, cells that need the largest amounts of energy, such as heart muscle cells and nerves, are affected the most by faulty mitochondria. The following passage comes from the United Mitochondrial Disease Foundation:

"Because mitochondria perform so many different functions in different tissues, there are literally hundreds of different mitochondrial diseases. [...] Because of the complex interplay between the hundreds of genes and cells that must cooperate to keep our metabolic machinery running smoothly, it is a hallmark of mitochondrial diseases that identical mtDNA mutations may not produce identical diseases."

Diseases that generate different symptoms but are due to the same mutation are referred to as genocopies. Conversely, diseases that have the same symptoms but are caused by mutations in different genes are called phenocopies. An example of a phenocopy is Leigh syndrome, which can be caused by several different mutations. Although symptoms of a mitochondrial disease vary greatly, they might include: loss of muscle coordination and weakness, problems with vision or hearing learning disabilities, heart, liver, or kidney disease, gastrointestinal problems, neurological problems, including dementia, Other conditions that are thought to involve some level of mitochondrial dysfunction, include: Parkinson's disease, Alzheimer's disease, bipolar disorder, schizophrenia chronic fatigue syndrome, Huntington's disease, diabetes & autism.

Key Points

  • The Krebs cycle is a series of chemical reactions used by all aerobic organisms to generate energy through the oxidization of acetate—derived from carbohydrates, fats, and proteins —into carbon dioxide.
  • Theoretically there are several alternatives to the TCA cycle, but the TCA cycle appears to be the most efficient.
  • The citric acid cycle consumes acetate (in the form of acetyl-CoA) and water, reduces NAD+ to NADH, and produces carbon dioxide.

Key Terms

  • acetyl CoA: Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for energy production.
  • citric acid cycle: An alternative name for the Krebs cycle.
  • glycolysis: The cellular degradation of the simple sugar glucose to yield pyruvic acid and ATP as an energy source.

Cellular Respiration: Glycolysis, Krebs Cycle, Electron Transport Chain:

The Krebs cycle uses the two molecules of pyruvic acid formed in glycolysis and yields high-energy molecules of NADH and flavin adenine dinucleotide (FADH2), as well as some ATP. The Krebs cycle occurs in the mitochondrion of a cell. Like the conversion of pyruvate to acetyl CoA, the citric acid cycle takes place in the matrix of the mitochondria. Almost all of the enzymes of the citric acid cycle are soluble, with the single exception of the enzyme succinate dehydrogenase, which is embedded in the inner membrane of the mitochondrion. Unlike glycolysis, the citric acid cycle is a closed loop: the last part of the pathway regenerates the compound used in the first step. The eight steps of the cycle are a series of redox, dehydration, hydration, and decarboxylation reactions that produce two carbon dioxide molecules, one GTP/ATP, and reduced forms of NADH and FADH2. This is considered an aerobic pathway because the NADH and FADH2 produced must transfer their electrons to the next pathway in the system, which will use oxygen. If this transfer does not occur, the oxidation steps of the citric acid cycle also do not occur. Note that the citric acid cycle produces very little ATP directly and does not directly consume oxygen.



Key Points

  • The Krebs cycle is a series of chemical reactions used by all aerobic organisms to generate energy through the oxidization of acetate—derived from carbohydrates, fats, and proteins —into carbon dioxide.
  • Theoretically there are several alternatives to the TCA cycle, but the TCA cycle appears to be the most efficient.
  • The citric acid cycle consumes acetate (in the form of acetyl-CoA) and water, reduces NAD+ to NADH, and produces carbon dioxide.

Key Terms

  • acetyl CoA: Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for energy production.
  • citric acid cycle: An alternative name for the Krebs cycle.
  • glycolysis: The cellular degradation of the simple sugar glucose to yield pyruvic acid and ATP as an energy source.

Steps in the Citric Acid Cycle

Step 1. The first step is a condensation step, combining the two-carbon acetyl group (from acetyl CoA) with a four-carbon oxaloacetate molecule to form a six-carbon molecule of citrate. CoA is bound to a sulfhydryl group (-SH) and diffuses away to eventually combine with another acetyl group. This step is irreversible because it is highly exergonic. The rate of this reaction is controlled by negative feedback and the amount of ATP available. If ATP levels increase, the rate of this reaction decreases. If ATP is in short supply, the rate increases.

Step 2. Citrate loses one water molecule and gains another as citrate is converted into its isomer, isocitrate.

Steps 3 and 4. In step three, isocitrate is oxidized, producing a five-carbon molecule, α-ketoglutarate, together with a molecule of CO2 and two electrons, which reduce NAD+ to NADH. This step is also regulated by negative feedback from ATP and NADH and by a positive effect of ADP. Steps three and four are both oxidation and decarboxylation steps, which release electrons that reduce NADto NADH and release carboxyl groups that form CO2 molecules. α-Ketoglutarate is the product of step three, and a succinyl group is the product of step four. CoA binds the succinyl group to form succinyl CoA. The enzyme that catalyzes step four is regulated by feedback inhibition of ATP, succinyl CoA, and NADH.

Step 5. A phosphate group is substituted for coenzyme A, and a high- energy bond is formed. This energy is used in substrate-level phosphorylation (during the conversion of the succinyl group to succinate) to form either guanine triphosphate (GTP) or ATP. There are two forms of the enzyme, called isoenzymes, for this step, depending upon the type of animal tissue in which they are found. One form is found in tissues that use large amounts of ATP, such as heart and skeletal muscle. This form produces ATP. The second form of the enzyme is found in tissues that have a high number of anabolic pathways, such as liver. This form produces GTP. GTP is energetically equivalent to ATP; however, its use is more restricted. In particular, protein synthesis primarily uses GTP.

Step 6. Step six is a dehydration process that converts succinate into fumarate. Two hydrogen atoms are transferred to FAD, producing FADH2. The energy contained in the electrons of these atoms is insufficient to reduce NAD+ but adequate to reduce FAD. Unlike NADH, this carrier remains attached to the enzyme and transfers the electrons to the electron transport chain directly. This process is made possible by the localization of the enzyme catalyzing this step inside the inner membrane of the mitochondrion.

Step 7. Water is added to fumarate during step seven, and malate is produced. The last step in the citric acid cycle regenerates oxaloacetate by oxidizing malate. Another molecule of NADH is produced.

Products of the Citric Acid Cycle

Two carbon atoms come into the citric acid cycle from each acetyl group, representing four out of the six carbons of one glucose molecule. Two carbon dioxide molecules are released on each turn of the cycle; however, these do not necessarily contain the most recently-added carbon atoms. The two acetyl carbon atoms will eventually be released on later turns of the cycle; thus, all six carbon atoms from the original glucose molecule are eventually incorporated into carbon dioxide. Each turn of the cycle forms three NADH molecules and one FADH2 molecule. These carriers will connect with the last portion of aerobic respiration to produce ATP molecules. One GTP or ATP is also made in each cycle. Several of the intermediate compounds in the citric acid cycle can be used in synthesizing non-essential amino acids; therefore, the cycle is amphibolic (both catabolic and anabolic).

Breakdown of Pyruvate

After glycolysis, pyruvate is converted into acetyl CoA in order to enter the citric acid cycle. In order for pyruvate, the product of glycolysis, to enter the next pathway, it must undergo several changes to become acetyl Coenzyme A (acetyl CoA). Acetyl CoA is a molecule that is further converted to oxaloacetate, which enters the citric acid cycle (Krebs cycle). The conversion of pyruvate to acetyl CoA is a three-step process. 

Step 1. A carboxyl group is removed from pyruvate, releasing a molecule of carbon dioxide into the surrounding medium. (Note: carbon dioxide is one carbon attached to two oxygen atoms and is one of the major end products of cellular respiration. ) The result of this step is a two-carbon hydroxyethyl group bound to the enzyme pyruvate dehydrogenase; the lost carbon dioxide is the first of the six carbons from the original glucose molecule to be removed. This step proceeds twice for every molecule of glucose metabolized (remember: there are two pyruvate molecules produced at the end of glycolysis); thus, two of the six carbons will have been removed at the end of both of these steps.

Step 2. The hydroxyethyl group is oxidized to an acetyl group, and the electrons are picked up by NAD+, forming NADH (the reduced form of NAD+). The high- energy electrons from NADH will be used later by the cell to generate ATP for energy.

Step 3. The enzyme-bound acetyl group is transferred to CoA, producing a molecule of acetyl CoA. This molecule of acetyl CoA is then further converted to be used in the next pathway of metabolism, the citric acid cycle.

Acetyl CoA and the Citric Acid Cycle

The citric acid cycle is a key component of the metabolic pathway by which all aerobic organisms generate energy. The name of this metabolic pathway is derived from citric acid, a type of tricarboxylic acid that is first consumed and then regenerated by this sequence of reactions to complete the cycle. The cycle consumes acetate (in the form of acetyl-CoA) and water, reduces NAD+to NADH, and produces carbon dioxide. The NADH generated by the TCA cycle is fed into the oxidative phosphorylation pathway. The net result of these two closely linked pathways is the oxidation of nutrients to produce usable energy in the form of ATP. Components of the TCA cycle were derived from anaerobic bacteria, and the TCA cycle itself may have evolved more than once. Theoretically there are several alternatives to the TCA cycle, however the TCA cycle appears to be the most efficient. If several alternatives independently evolved, they all rapidly converged to the TCA cycle. The citric acid cycle is a key component of the metabolic pathway by which all aerobic organisms generate energy. Through the catabolism of sugars, fats, and proteins, a two carbon organic product acetate in the form of acetyl-CoA is produced. Acetyl-CoA along with two equivalents of water (H2O) are consumed by the citric acid cycle, producing two equivalents of carbon dioxide (CO2) and one equivalent of HS-CoA. In addition, one complete turn of the cycle converts three equivalents of nicotinamide adenine dinucleotide (NAD+) into three equivalents of reduced NAD+ (NADH), one equivalent of ubiquinone (Q) into one equivalent of reduced ubiquinone (QH2), and one equivalent each of guanosine diphosphate (GDP) and inorganic phosphate (Pi) into one equivalent of guanosine triphosphate (GTP). The NADH and QH2 that is generated by the citric acid cycle is used by the oxidative phosphorylation pathway to generate energy-rich adenosine triphosphate (ATP). One of the primary sources of acetyl-CoA is sugars that are broken down by glycolysis to produce pyruvate that, in turn, is decarboxylated by the enzyme pyruvate dehydrogenase. This generates acetyl-CoA according to the following reaction scheme:

CH3C(=O)C(=O)O– (pyruvate) + HSCoA + NAD+ → CH3C(=O)SCoA (acetyl-CoA) + NADH + H+ + CO2

By | 2019-05-31T14:20:08+01:00 May 31st, 2019|Blog|Comments Off on Mitochondria, ATP, Glycolysis & Krebs Cycle
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